Process for producing L-cysteine or its derivatives

Abstract

L-cysteine and derivatives thereof of the formula (I): RS-CH2CHCOOH (I) ¦ NH2 wherein R is selected from the group consisting of hydrogen, C1-C15 alkyl, C2-C15 alkenyl, C6-C15 aryl, C7-C15 aralkyl, are prepared by a process which comprises reacting beta -substituted L-alanine having the formula (II): X-CH2CHCOOH (II) ¦ NH2 wherein X is selected from the group consisting of halogen, -OR' and -SR'; wherein R' is selected from the group consisting of hydrogen, allyl, C1-C15 alkyl, C6-C15 aryl and C7-C15 aralkyl, with a thiol, or hydrogen sulfide, of the formula (III):

What is claimed as new and intended to be covered by letters patent is: 
     
       1. A process for producing L-cysteine and derivatives thereof of the formula (I): ##EQU3## wherein R is selected from the group consisting of hydrogen, C 1  - C 15  alkyl, C 2  - C 15  alkenyl, C 6  - C 15  aryl, C 7  - C 15  aralkyl, which comprises reacting β-substituted-L-alanine having the formula (II): ##EQU4## wherein X is selected from the group consisting of halogen, --OR' and --SR', erein R' is selected from the group consisting of hydrogen, allyl, C 1  - C 15  alkyl, C 6  - C  15  aryl and C 7  - C 15  aralkyl, with a thiol, or hydrogen sulfide, of the formula (III):   r -- sh                                                    (iii)     wherein R is as defined above, ammonium hydrosulfide or a metal hydrosulfide of the formula (IV):     r -- s -- y                                                (iv)     wherein R is hydrogen, and Y is ammonium or a metal, in an aqueous medium, in the presence of cysteine desulfhydrase.   
     
     
       2. The process of claim 1, wherein L-cysteine is produced by the reaction of β-substituted L-alanine of the formula (II) with a compound selected from the group consisting of hydrogen sulfide, ammonium hydrosulfide, a water-soluble metal hydrosulfide of the formula (IV), ammonium sulfide whereby ammonium hydrosulfide and/or hydrogen sulfide is produced in the aqueous medium, and a metal sulfide whereby said metal hydrosulfide and/or hydrogen sulfide is produced in the aqueous medium. 
     
     
       3. The process of claim 1, wherein the derivative of L-cysteine of the formula (I) is produced by the reaction of β-substituted L-alanine of the formula (II) with a thiol of the formula (III). 
     
     
       4. The process of claim 1, wherein R is selected from the group consisting of hydrogen, C 1  - C 5  alkyl and C 2  - C 5  alkenyl. 
     
     
       5. The process of claim 4, wherein R is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl and allyl. 
     
     
       6. The process of claim 1, wherein R' is selected from the group consisting of hydrogen, allyl, and C 1  - C 5  alkyl. 
     
     
       7. The process of claim 6, wherein R' is selected from the group consisting of hydrogen, allyl and methyl. 
     
     
       8. The process of claim 1, wherein X is chlorine. 
     
     
       9. The process of claim 1, wherein ammonium sulfide which produces ammonium hydrosulfide and/or hydrogen sulfide in the aqueous medium or a water-soluble metal sulfide which produces a water-soluble metal hydrosulfide and/or hydrogen sulfide in the aqueous medium, is employed instead of hydrogen sulfide, ammonium hydrosulfide or a water-soluble metal hydrosulfide. 
     
     
       10. The process of claim 9, wherein said metal sulfide is selected from the group consisting of a sulfide of an alkali metal and an alkaline earth metal. 
     
     
       11. The process of claim 10, wherein said metal sulfide is selected from the group consisting of sodium sulfide, potassium sulfide, calcium sulfide and barium sulfide. 
     
     
       12. The process of claim 1, wherein said metal hydrosulfide is water-soluble. 
     
     
       13. The process of claim 12, wherein said metal hydrosulfide is selected from the group consisting of a hydrosulfide of an alkali metal and an alkaline earth metal. 
     
     
       14. The process of claim 13, wherein said metal hydrosulfide is selected from the group consisting of sodium hydrosulfide and potassium hydrosulfide. 
     
     
       15. The process of claim 1, wherein cysteine desulfhydrase is derived from a microorganism selected from the group consisting of Brevibacterium, Sarcina, Corynebacterium, Arthrobacter, Pseudomonas, Proteus, Micrococcus, Escherichia, Serratia, Alcaligenes, Bacillus, Agrobacterium, Enterobacter (Aerobacter), Citrobacter, Klebsiella and Salmonella. 
     
     
       16. The process of claim 1, wherein the reaction is carried out at a temperature of 30° - 50°C for a period of 2 - 48 hours in an aqueous medium having a pH of 7 - 11. 
     
     
       17. The process of claim 1, wherein 1 - 5 g/l of dried cells containing cysteine desulfhydrase is employed. 
     
     
       18. The process of claim 1, wherein the concentrations of β-substituted L-alanine, and the thiol, hydrogen sulfide, ammonium hydrosulfide or metal hydrosulfide are each 3 - 20 weight percent. 
     
     
       19. The process of claim 1, wherein said aqueous medium additionally contains a carbonyl compound containing 1 to 20 carbon atoms in a concentration of from 0.05 - 10 M. 
     
     
       20. The process of claim 19, wherein said carbonyl compound is selected from the group consisting of an α-keto carboxylic acid containing 3 to 20 carbon atoms, an aldehyde containing 1 to 20 carbon atoms, and a ketone containing 3 to 20 carbon atoms. 
     
     
       21. The process of claim 20, wherein said α-keto carboxylic acid, aldehyde or ketone is selected from the group consisting of benzaldehyde, isobutyraldehyde, acetone, methyl isobutyl ketone, methyl ethyl ketone, cyclohexanone, benzophenone, benzil, pyruvic acid, 2-oxobutyric acid and 2-oxoglutaric acid. 
     
     
       22. The process of claim 1, wherein said reaction is carried out in the presence of pyridoxal phosphate in a concentration of up to 0.01 mM.